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Biomedical subjects

N Matsubara

Publications and source records attributed to N Matsubara.

17 recordsLinked to original sources
PubMed1992

On the mechanism of a mammalian neuronal type nicotinic acetylcholine receptor investigated by a rapid chemical kinetic technique. Detection and characterization of a short-lived, previously unobserved, main receptor form in PC12 cells.

The mammalian nicotinic acetylcholine receptor in PC12 cells has many properties characteristic of the neuronal receptors involved in key chemical reactions that are responsible for signal transmission between cells of the nervous system. This report describes initial investigations of the mechanism of this receptor using a rapid chemical kinetic technique with a time resolution of 20 ms, which represents a 250-fold improvement over the best time resolution (5 s) employed in previous studies. Carbamoylcholine, a stable analogue of the neurotransmitter acetylcholine, was the activating ligand used, and the concentration of open transmembrane receptor-channels in PC12 cells was measured by recording whole-cell currents at pH 7.4, 21-23 degrees C, and a transmembrane voltage of -60 mV. Two receptor forms that account for 80% and 20% of the receptor-controlled current were detected; the main receptor form, accounting for 80% of the whole-cell current, desensitized completely before the first measurements had been made in previous studies. Only the main receptor form has been investigated so far using the new method. The constants of a mechanism that accounts for the concentration of the open transmembrane receptor-channel over a 100-fold range of carbamoylcholine concentration were evaluated: the dissociation constant of the site controlling channel opening (K1 = 2.0 mM), the channel-opening equilibrium constant (phi -1 = 5.0), and the dissociation constant of an inhibitory site to which carbamoylcholine binds (KR = 6.5 mM). These evaluated constants allow one to calculate Po, the conditional probability that at a given concentration of carbamoylcholine the receptor-channel is open. Po was also determined in the presence of 2 mM carbamoylcholine by an independent method, the single-channel current-recording technique, and the agreement between the Po values obtained in two independent ways is within experimental error. This result indicates that the time resolution of the chemical kinetic technique employed was sufficient to evaluate the constants pertaining to the active state of the receptor, which forms a transmembrane channel, before its conversion to desensitized receptor forms with different properties. Previous kinetic measurements with a time resolution of 5 s showed that many compounds, such as anesthetic-like molecules, nerve growth factor, and substance P, modify the function of the neuronal receptor in PC12 cells or react specifically with the neuronal but not with the muscle receptor, for example, some toxins.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

How fast does an acetylcholine receptor channel open? Laser-pulse photolysis of an inactive precursor of carbamoylcholine in the microsecond time region with BC3H1 cells.

The integrated function of the nervous system depends on specific and rapid transmission of signals between its constituent cells. The nicotinic acetylcholine receptor is the best known of a group of membrane-bound proteins responsible for such transmission; for this process to occur, a specific neurotransmitter, in this case acetylcholine, must bind to the receptor, which then forms transmembrane channels through which cations pass. The resulting change in transmembrane voltage determines whether or not a signal is transmitted. The question of how fast this process takes place in any neurotransmitter receptor has remained one of the interesting and most challenging in the field. To answer it, many attempts have been made to evaluate the rate constant for the opening of the acetylcholine receptor channel, but in almost all these studies the rate was measured after the receptor-mediated reaction, which involves the open channel and many intermediate states, had reached a quasi equilibrium. This resulted in a plethora of reported values for the rate constant that differ by a factor of up to 50-fold, even when the measurements were made with the same type of cell. The new approach described here involves the use of single cells of a mammalian cell line (BC3H1), containing muscle-type acetylcholine receptors, and the rapid introduction of neurotransmitter to the cell surface. The rapid delivery was achieved by converting a previously synthesized photolabile precursor of carbamoylcholine to carbamoylcholine, a stable amino-group-containing analogue of acetylcholine, with a single laser pulse and an observed photolysis rate of 7300 s-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Peritoneal mesothelioma: hypertrophic gastroepiploic and omental arteries identified by radioimmune angiography.

We report a first case of malignant peritoneal mesothelioma examined by radioimmune (RI) angiography with technetium-99m human serum albumin. The RI angiography clearly demonstrated the characteristic findings including hypertrophic gastroepiploic arteries and dilated omental branches. These findings may be very helpful in distinguishing malignant peritoneal mesotheliomas from peritoneal carcinomatosis.

Adult↗
PubMed1992

Anti-proliferative effect on human pancreatic cancer cells of natural human tumour necrosis factor-beta combined with natural human interferon-alpha or interferon-gamma.

The anti-proliferative effects of natural cytokines, human tumour necrosis factor-beta, natural human interferon-alpha and natural human interferon-gamma, on three human pancreatic cancer cell lines (PANC-1, MIA PaCa-2 and BxPC-3) were investigated in vitro. The anti-proliferative effect was determined using the dye uptake method and analysed for synergism by the median effect principle. Tumour necrosis factor-beta, as a single agent, had little anti-proliferative effect on any of the three cell lines, whereas interferon-alpha and interferon-gamma exhibited a strong anti-proliferative effect against two cell lines (MIA PaCa-2 and BxPC-3) and one cell line (BxPC-3), respectively. When tumour necrosis factor-beta and interferon-alpha were administered together (ratio 1:1), a synergistic effect was observed against PANC-1 cells. The combination of tumour necrosis factor-beta and interferon-gamma (ratio 10:1) was synergistic against both PANC-1 and MIA PaCa-2 cells. A synergistic anti-proliferative effect of tumour necrosis factor-beta and interferons was, therefore, observed even for cell lines that showed little biological response to each cytokine alone. The data suggest that some future improvement in the treatment of pancreatic cancer may be obtained by using combination cytokine therapy.

Cell Division↗
PubMed1992

Chemotherapy in small cell lung cancer--from view point of dose intensity.

Results of chemotherapy trials for small cell lung cancer carried out for the past 5 years were analyzed from view point of dose intensity. Early study of CDDP+EP+ADM (1985 to 1987) showed moderate response rate (RR) of 72% with MST of 369 days. Succeeding alternative protocol of CDDP+EP+VCR/CPM+ADM+MTX (1989-1990) showed improved RR of 88% and MST of 13 months. Actual dose and interval for the alternating regimen was superior to the single arm regimen. Projected relative dose intensity against MAOP protocol including 6 drugs common to our regimen was 0.86 and delivered RDI was 0.61 with comparable RR and MST. The results may indicate that change of dose intensity within the conventional range does not result in major advantage or disadvantage for substantial prolongation of the survival in SCLC patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

[Clinical significance of respiratory infections associated with lung cancer patients].

An attempt was made to interpret the clinical significance of secondary infections associated with lung cancer. The incidence of secondary infections was 51.4% in 214 in-patients with lung cancer in our institution in 1988 and 1989, and almost all of them had respiratory infections caused by commonly encountered bacteria. The incidence of infection was high in lung cancer of cell types other than adenocarcinoma, and in those with hypoalbuminemia, impaired cellular immunity and obstruction of the airway. The prognosis in patients with infection was much poorer than that in patients without infection. Major pathogens responsible for infection were Staphylococcus aureus including methicillin-resistant S. aureus (MRSA), Haemophilus influenzae, Klebsiella spp. and Pseudomonas aeruginosa. These pathogens, except for H. influenzae, were isolated in the terminal stage in cases with airway obstruction and post cancer chemotherapy. The efficacy rate of 194 therapeutic regimens against infection was 57.7%. It was thus found that the efficacy rate in 1988 and 1989 exceeded that in the 1970s. The effectiveness was very poor for infections caused by S. aureus and P. aeruginosa, and for cases with airway obstruction and marked impairment of pulmonary blood flow. The efficacy rate of single-drug regimens was 57.1% (80/140) and that of combined regimens was 59.3% (32/54). The above results indicate that a new combined therapy which includes a beta-lactam antibiotic as well as measures to improve the general health of compromised hosts are required in the treatment of secondary infections in these patients.

Adult↗
PubMed1991

Antibody to a zinc finger protein in a patient with paraneoplastic cerebellar degeneration.

In some patients with paraneoplastic cerebellar degeneration (PCD), autoantibodies against neural components have been identified. Here, we demonstrate a major 58 kd protein antigen in an immunoblot of human cerebellum by serum from a patient with PCD. Immunohistochemically, the serum recognized neural cells especially Purkinje cells in a human brain. To identify the details of the target antigens for the antibody, we isolated a cDNA clone from a human cerebellar library. Homology searches revealed a similarity with the zinc finger proteins. PCD related proteins reported here may be important to maintain neural cells especially those in the cerebellum, and further studies on this molecule may help us elucidate the causes of degenerative or autoimmune diseases in the cerebellum.

Aged↗
PubMed1991

The possible involvement of free radical scavenging properties in the actions of cytokines.

Among the cytokines which show an antiproliferative effect on certain tumor cells, we investigated the free radical scavenging properties of tumor necrosis factor-alpha, interferon-alpha, and interferon-gamma. The scavenging properties were determined in vitro by the ability to reduce DPPH free radicals. All of these cytokines exhibited marked DPPH free radical scavenging ability.

Bepridil↗
PubMed1991

Production of hydroxyl radicals by tumor cells varies with cell type as measured by electron spin resonance spectrometry.

The hydroxyl radicals produced by two adherent cell lines, a human cancer cell and a mouse fibroblast, and six suspended human leukemia cell lines at different stages of differentiation were measured by electron spin resonance (ESR) spectrometry. The concentration of hydroxyl radicals detected in these tumor cells increased in proportion to temperature and cell number. The addition of the enzymes superoxide dismutase (SOD) and catalase (which do not permeate the cell membrane), reduced the amount of hydroxyl radicals detected. SOD decreased hydroxyl radicals somewhat but catalase eliminated hydroxyl radicals almost completely. These findings suggest that hydroxyl radicals are produced extracellularly consisted primarily of H2O2 but partially from superoxide radicals. Using the human leukemia cell lines at different stages of differentiation we demonstrated that cell differentiation may correlate with hydroxyl radical production. The earlier the stage of leukemic cell differentiation the more the greater the production of hydroxyl radicals. Moreover, the ability of SOD or catalase to eliminate hydroxyl radical activity correlated inversely with leukemic cell differentiation.

Animals↗
PubMed1979

Carcinogenicity examination of betel nuts and piper betel leaves.

A dry powder of betel nuts, piper betel leaves and lime was administered to rats. Epidermal thickening was frequently observed in the upper digestive tracts of rats in groups fed the betel nut diet mixed with lime and the betel leaves diet, and a forestomach papilloma was seen in 1 rat given betel leaves diet. These epidermal changes were scarcely seen in rats given either betel nut or normal diet alone.

Animals↗
PubMed1979

Alpha-fetoprotein producing rhabdomyosarcoma of the adult liver.

An autopsy case of a rare primary tumor in a 76-year-old man is described. The tumor is histologically comprised of rhabdomyoblasts massively infiltrating without any epithelial elements referable to be as hepatoma. There was no evidence that regarded the hepatic tumor as metastatic secondary tumor in histological examination of other organs. Furthermore, interesting was the production of alpha-fetoprotein from the tumor cells that was detected by immunofluorescent antibody technique. Review of the literature on primary liver rhabdomyosarcomas or adult hepatoblastomas shows no similar case.

Aged↗
PubMed1979

In vitro antibacterial activity of cefoperazone (T-1551), a new semisynthetic cephalosporin.

Cefoperazone, a new semisynthetic cephalosporin, has a broad spectrum of antibacterial activity. It is as active as cefazolin and cefamandole against gram-positive bacteria and is more active than cefazolin and cefamandole against such gram-negative bacilli as Escherichia coli, Klebsiella pneumoniae, Proteus species, Pseudomonas aeruginosa, Citrobacter freundii, Enterobacter cloacae, and Serratia marcescens. The superiority of cefoperazone over cefazolin and cefamandole with respect to activity against P. aeruginosa by more than 200-fold was especially remarkable. As with other beta-lactam antibiotics, there was only a small spread between the minimum inhibitory concentrations and the minimum bactericidal concentrations of cefoperazone and a significant decrease in activity with an increase in inoculum size. Activity was not altered significantly by the addition of human serum to the test medium. Cefoperazone is relatively stable to hydrolysis to beta-lactamases produced by gram-negative bacteria. Relative rates of hydrolysis of cefoperazone by cephalosporinases are 7.0 to 0.01, with reference to cephaloridine hydrolysis (base, 100). Cefoperazone is also more stable than penicillin G and cephaloridine to various types of penicillinases.

Bacteria↗
PubMed1979

Induction of hepatic tumors in rats by senkirkine and symphytine.

The carcinogenicity of the pyrrolizidine alkaloids senkirkine and symphytine was studied in male inbred ACI rats. Animals were divided into 3 groups: Group I received ip injections of freshly prepared senkirkine at a dose of 10% of the median lethal dose (LD50) twice weekly for 4 weeks and then once a week for 52 weeks. Group II received ip injections of symphytine at a dose of 10% of the LD50 by the same injection schedule as in group I. The control group was given ip injections of a 0.9% NaCl solution following the same injection schedule as in experimental groups. All group I rats survived for more than 290 days after the start of injections, and 9 of 20 rats developed liver cell adenoma. All group II animals survived for more than 330 days after the start of injections. Of 20 rats, 4 had liver tumors, 3 had hemangioendothelial sarcomas, and 1 had liver cell adenoma. The hemangioendothelial sarcomas showed metastasis in the lungs of 2 rats. The control group had no liver tumors.

Animals↗
PubMed1978

Effect of colostomy on intestinal carcinogenesis by methylazoxymethanol acetate in rats.

The effect of the fecal stream on the induction of intestinal tumors was studied in 3 groups of SD rats. Rats in group 1 were subjected to single-barreled colostomies for the complete exclusion of the fecal stream at the proximal one-third level of the colons and were given consecutive iv injections of methylazoxymethanol acetate. Rats in group 2 were given methylazoxymethanol acetate alone. Rats in group 3 were not treated and served as controls. Tumors were noted in the small and large intestines of almost all rats in both groups 1 and 2. Even animals with single-barreled colostomies frequently developed tumors in the colon distal to the colostomy where the mucosa did not have contact with the fecal stream. These results indicated that carcinogens could probably reach the intestinal mucosa via the vascular system as well as by biliary transport.

Animals↗
PubMed1976

Purification and some properties of NADP+ -specific isocitrate dehydrogenase from an extreme thermophile, Thermus flavus AT-62.

Thermostable NADP+ -specific isocitrate dehydrogenase (EC 1.1.1.42) was purified from crude extract of an extremely thermophilic bacterium Thermus flavus AT-62 through DEAE-cellulose column, acetone fractionation, DEAE-Sephadex A-50 column and isoelectric focussing. The enzyme was purified about 500-folds in its specific activity and purity was found to be about 96%. The enzyme was not inactivated after 60 min at 70 degrees C, but 20 and 80% of the activity were lost after 60 min at 80 degrees and 90 degrees C, respectively. Oxalacetate plus glyoxylate (each 1 nM) demonstrated 75% inhibition of the activity in concerted manner. The degree of the inhibition and the affinity of the enzyme for isocitrate and NADP+ decreased with the rise of temperature, especially above 60 degrees C. The activation energy below and above 60 degrees C were 14,500 and 8,000 cal per mole respectively. In CD spectra negative bands at 210 and 220nm were observed and alpha-helix content was calculated to be about 26%. In the course of heating up to 60 degrees practically no change in CD bands are observed, but above 60 degrees the depth of CD bands decreased gradually and remarkably above 80 degrees C. The effect of temperature on kinetic parameters and secondary structures of the enzyme was discussed in relation to the temperature adaptation of the organism.

Circular Dichroism↗